Infections in the post-transplant period are a leading cause of morbidity and mortality among solid organ transplant recipients and hematopoietic stem cell transplant recipients. In the last 6 years we have completed a prospective 23 center surveillance network (TRANSNET), screening over 34,000 transplant recipients and identifying over 2100 proven and probable cases of invasive fungal infection (IFI). These data have led to improved understanding of the disease burden in the U.S. and has highlighted some of the major differences among transplant groups. Despite its value as a measure of disease burden, TRANSNET had limited ability to perform case-control trials of important risk factors. The CDC- sponsored initiative Organ Transplant Infection Detection and Prevention Program (2004-2009) was a timely and necessary next step toward the assessment of risk factors associated with the development of IFls, and to initiate prospective surveillance for important non-fungal pathogens. Our success in this program can be measured by the large numbers of patients enrolled into 2 cohorts (lung transplant recipients and allogeneic stem cell transplant recipients) from 3 sites, and the diverse types of infection observed among each of these two high risk groups. In this proposal, we propose to achieve the following aims: 1) to perform prospective surveillance among selected OTRs and HSCTs for proven and probable IFls at 3 US transplant centers (University of Alabama at Birmingham, University of Michigan, and University of Pennsylvania); 2) to perform case-control studies among patients at high risk for invasive mould infections to identify significant nosocomial and outpatient risk factors and to establish recommendations for prevention; 3) to develop methodologies for conducting prospective surveillance for selected non-fungal pathogens (i.e. C.difficile, cytomegalovirus, West Nile virus, respiratory viruses, and selected multiresistant bacteria); and 4) to establish a bank for fungal isolates and other clinical specimens. The achievement of these goals will provide critically important insights into the key modifiable risk factors associated with the development of IFls and other post-transplantation infectious complications in especially high-risk patients. Moreover, the establishment of standard surveillance methodology across multiple sites will significantly improve the quality and ease of data collection for important pathogens. Finally, the establishment of a bank will be invaluable in the development and validation of newer diagnostic assays. PUBLIC HEALTH RELEVANCE: Organ and hematopoietic stem cell transplantation has become an increasingly important and life saving measure for thousands of persons each year in the United States. Organ rejection, graft vs. host disease, and post-transplantation infections complications, especially invasive fungal infection, are the key factors related to morbidity and mortality in this population. Important questions remain concerning invasive fungal infections in transplant recipients, including determining the real burden of disease and identifying key risk factors associated with development of these complications. Moreover, the emergence of new non-fungal pathogens, especially C. difficile colitis, West Nile virus, other respiratory viruses, and multiresistant bacteria, dictates renewed focus on the post-transplant period. Thus, the Organ Transplant Infection Detection and Prevention Program (OTIP) is a timely and important initiative put forth by the CDC to address some of the more important issues in these patients. This application involves three large, well-integrated transplant programs (University of Alabama at Birmingham, University of Michigan and University of Pennsylvania) with strong experience in prospective surveillance and excellent record of collaboration. This consortium is very well positioned to accomplish the goals set forth in this announcement.